Process fob the manufacture of



Patented Sept. 4, 1945 PROCESS FOR THE MANUFACTURE OF PYRIDINE DERIVATIVES v Otto Sehnider, Basel, Switzerland, assignor to 1 Hoflmann-La Roche Inc., Nutley, N. 1., a corporation of New Jersey Original application September 5,

No Drawing.

1941, Serial No. 409,750. Divided and this application April 28, 1944, Serial No. 533,253. In Switzerland November 1, 1940 3Claims.

Pyridine derivatives of the general formula onion HO-L CH:

cyanacetic acid amide at moderately elevated a temperature in the presence of a' condensing agent.

The present invention relates to a new process for the manufacture of the said 2-methy1-4- ethoxymethyl-S-cyano-B-hydroxypyridine derivatives of the above general formula. It has been found that by reacting 2-amino-4-oxo-5-alkoxypentene (2) with cyano-acetamide 2-methyl-4- alkoxymethyl-S-cyano-B-hydroxy-Drridine may be obtained.

The compound 2-smino-4-oxo-5-alkoxypentens-(2) used as one of the starting materials may be prepared from alkoxy-acetyl-acetone by the action of ammonia thereon. Preferably, the 5- ethoxypentene-(2) derivative maybeused. other lower alkyl groups may, however, take the place of the ethyl radical. It may, further, in some instances be unnecessary to isolate the 2-amin'o- 4-oxo-5-ethoxypentene-(2) because surprisingly the reaction with certain derivatives of malonlc acid or cysnscetie acid occurs equally well in aqueousandnon-aqueous solutions.

As the second starting material cyano-acetamide of the formula HsNOO-CHs-CN may be used. It is helpful to add a solvent and to heat the reaction mixture.

The following example shows in detail methods for the execution of the invention, without, however, limiting its scope thereto.

Example A mixture of 143 parts by weight of 2-amino- 4-oxo-5-etho1w-pentene-(2) and 84 parts by weight of cyano-acetamide is heated. At about 120 C. ammonia is slowly evolved and a homogeneous solution is obtained. The temperature is slowly raised to 140-450 C. when the separation of ammonia becomes more and more intensive. After some time 2-methyl-4-ethoxy-methyl-5- cyano-B-hydroxy-pyridine besins to crystallise.

When the separation of ammonia has ceased, on

keeping the temperature constantly between lilo-150 C., which is the case after 1 /2 to 2 hours, the reaction is complete. 0n coolin 2-methyl- 4-ethoxymethyl-5-cyano-6-hydroxy-py idine solidifies completely. It can be purified by dissolving in a dilute solution of caustic soda and precipitation with an acid or by crystallisation from ethyl-alcohol. It melts at 210 C.

The reaction succeeds in the same way if anisole is used as solvent.

I claim:

1. In a process for the manufacture of 2-methyl- 4-alkoxy-methyl-fi-cyano-G-hydroxy-pyridine the step comprising reacting 2-amino-4-oxo-5- alkoxy-pentene-QL with cyanoacetamide.

2. In a rocess for the manufacture of 2-methyl-4-alkoxy-methyl-5-cyano-6-hydroxy -pyridine the step comprising reacting 2-amino-4-oxo-6- alkoxy-pentene (2) with cyanoacetamide at elevated temperature in the presence of a solvent:

3. In a process for the'manufacture of fl-methyl-4-alkon-methyl-5-cyano-6-hydroxy -D7ridine the step comprising reacting 2-amino-4-oxc-5- ethoxy-pentene-(2) with cysnoacetamide at elevated temperature in the presence of a solvent. 

